Evaluation of potential immune response and in vivo survival of riboflavin-ultraviolet light-treated red blood cells in baboons.
BACKGROUND
Pathogen reduction methods have the potential to modify blood components, resulting in immunologic reactions or compromised blood components. This study evaluated the hypothesis that there is no immune response to riboflavin-and-ultraviolet [UV]-light-treated red blood cells (RBCs), as observed by serology and by survival of RBCs in circulation.


METHODS
Three baboons were in each treatment group: 1) untreated (negative control), 2) quinacrine mustard (QM)-treated (positive control), and 3) riboflavin-and-UV light-treated (test group) RBCs. In the immunization phase, autologous test or control RBCs were injected subcutaneously on Days 0, 21, 42, and 49. Plasma samples from these days were tested against test or control RBCs by flow cytometry and standard serology. On Day 56, autologous (51)Cr-labeled test or control RBCs were injected. Blood samples were taken over 21 days after injection to determine RBC survival (t(1/2)).


RESULTS
Untreated and riboflavin-and-UV-light-treated RBCs showed no evidence of significant immunoglobulin G (IgG) binding after incubation with autologous plasma. RBC-bound IgG was detected on QM-treated RBCs after incubation with autologous plasma. This antibody was inhibited by QM, as demonstrated by a hapten inhibition study. t(1/2) values for the untreated and riboflavin-and-UV-light-treated RBCs were 7.3 +/- 0.8 and 7.5 +/- 1.7 days, respectively; the t(1/2) value for QM-treated RBCs was 2.3 +/- 2.9 days.


CONCLUSIONS
Treatment with riboflavin and UV light did not render RBCs immunogenic. Positive controls indicated that immunization promoted an immune response. In the (51)Cr-labeled RBC survival phase of the study, riboflavin-and-UV-light-treated RBCs exhibited behavior similar to negative control RBCs. Detrimental immunologic or functional side effects were not observed.
Goodrich
Raymond P
RP
Navigant Biotechnologies, Lakewood, Colorado 80227, USA. ray.goodrich@navigantbiotech.com
Murthy
Krishna K
KK
Doane
Suzann K
SK
Fitzpatrick
Christy N
CN
Morrow
La Shayla
LS
Arndt
Patricia A
PA
Reddy
Heather L
HL
Buytaert-Hoefen
Kimberley A
KA
Garratty
George
G
D000818:Animals; D001804:Blood Transfusion, Autologous; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D004203:Disinfection; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D048548:Papio cynocephalus; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D012256:Riboflavin / Q000009:adverse effects / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects
D007074:Immunoglobulin G; D017319:Photosensitizing Agents; D012256:Riboflavin